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Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Combined effect of sodium selenite and docetaxel on PC3 metastatic prostate cancer cell line
Mariana Freitas1, Vera Alves, Ana Bela Sarmento-Ribeiro
1General Pathology Laboratory, Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal. freitas.mariana@gmail.com
Abstract:
Docetaxel and sodium selenite are well known for their anticancer properties. While resistance to docetaxel remains an obstacle in prostate cancer chemotherapy, sodium selenite, has been exploited as a new therapeutic approach. Currently, development of therapies affecting a multitude of cell targets, have been proposed as a strategy to overcome drug resistance. This association may reduce systemic toxicity counteracting a wide range of side effects. Here we report the effect of docetaxel and sodium selenite combination on the PC3 prostate cancer cell line, derived from bone metastasis. Therefore we evaluate cell growth, cell cycle progression, viability, mitochondria membrane potential, cytochrome C, Bax/Bcl2 ratio, caspase-3 expression and reactive oxygen species production. Our results suggest that sodium selenite and docetaxel combination have a synergistic effect on cell growth inhibition (67%) compared with docetaxel (22%) and sodium selenite (24%) alone. This combination also significantly induced cell death, mainly by late apoptosis vs necrosis, which is correlated with mitochondria membrane potential depletion. On the other hand, cytochrome C, Bax/Bcl2 ratio and caspase-3, known as proapoptotic factors, significantly increased in the presence of sodium selenite alone, but not in the presence of docetaxel in monotherapy or in combination with sodium selenite. These findings suggest that docetaxel and sodium selenite combination may be more effective on prostate cancer treatment than docetaxel alone warranting further evaluation of this combination in prostate cancer therapeutic approach.
Insights
Combining docetaxel and sodium selenite shows synergistic effects against prostate cancer cells, significantly inhibiting growth and inducing apoptosis. This combination therapy may offer a more effective treatment approach than docetaxel alone.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Docetaxel is a key chemotherapy for prostate cancer, but resistance is a significant challenge.
- Sodium selenite presents a novel therapeutic strategy with anticancer properties.
- Combination therapies targeting multiple cellular pathways are crucial for overcoming drug resistance.
Purpose of the Study:
- To investigate the synergistic effects of combining docetaxel and sodium selenite on the PC3 prostate cancer cell line.
- To evaluate the impact of this combination on cell growth, cell cycle, viability, and apoptotic pathways.
Main Methods:
- PC3 prostate cancer cells were treated with docetaxel, sodium selenite, or their combination.
- Assays included cell growth, cell cycle progression, viability, mitochondrial membrane potential, cytochrome C, Bax/Bcl2 ratio, caspase-3 expression, and reactive oxygen species production.
Main Results:
- The combination of sodium selenite and docetaxel demonstrated a synergistic effect, inhibiting cell growth by 67%, compared to 22% for docetaxel and 24% for sodium selenite alone.
- The combination significantly induced cell death, primarily through late apoptosis, linked to mitochondrial membrane potential depletion.
- While sodium selenite alone increased proapoptotic factors (cytochrome C, Bax/Bcl2 ratio, caspase-3), the combination did not show this effect.
Conclusions:
- Docetaxel and sodium selenite combination exhibits synergistic anticancer activity against prostate cancer cells.
- This combination induces cell death via apoptosis and may overcome docetaxel resistance.
- Further research into this combination as a prostate cancer therapeutic approach is warranted.
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